The development of the Clinical and Translational Science Center (CISC) fulfills the mission to advance the nation's clinical research enterprise of moving translational research seamlessly from bench to bedside and to the community. The Center represents our vision to deliver the vast knowledge of recent biomedical advances to clinical application for meaningful healthcare practices and to nurture multidisciplinary translational research education and training. The CTSC has been designed to capture the collective of intellectual capital, cutting-edge resources and diverse patient base of partnering institutions and to integrate them for maximum translational research benefits. As lead institution, Weill Cornell Medical Center (WCMC) will serve as an academic home through which essential resources, technological tools and education programs can be efficiently shared and managed. The partner institutions comprising the CTSC are also neighbors located on York Avenue. Within the immediate area are: WCMC, including Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences and the Weill Cornell Campus of NewYork-Presbyterian Hospital; Memorial Sloan-Kettering Cancer Center; and the Hospital for Special Surgery. In close proximity on the East Side of Manhattan are: Hunter College School of Nursing, Hunter College Center for the Study of Gene Structure and Function/Research Center for Minority Institutions and the Cornell University Cooperative Extension in New York City. The resulting cluster of institutions forms a unique and cohesive biomedical complex fulfilling the NIH roadmap initiative of breaking-down institutional and disciplinary silos to accelerate translational research. Separately, the partner institutions are superb centers of intellectual and academic excellence, thus their integration into the CTSC will harness their distinctive characteristics and hasten clinical and translational research breakthroughs for improved patient care. The trans-institutional governance structure outlined in this application and supplemented by a comprehensive systems-based evaluation process are important in overcoming bureaucracies and barriers. New initiatives were sculpted and programs with a history of collaboration between partners were broadened and restructured. The key elements of the CTSC are: 1) development of novel clinical and translational methodologies; 2) pilot and collaborative translational and clinical studies; 3) biomedical informatics; 4) design, biostatistics and clinical research ethics; 5) regulatory knowledge and support; 6) participant and clinical interaction resources; 7) community engagement and research; 8) translational technologies and resources; 9) research education, training and career development; and 10) other program functions. The CTSC is a vital link between the academic, research and clinical practice functions of partner institutions and will provide an important continuum in translational research.